Caffeine Toxicity

Caffeine toxicity causes vomiting, tremor, tachycardia, hypokalaemia, hyperglycaemia, seizures and ventricular arrhythmia. It is most often caused by powdered or tablet caffeine, energy products and supplements, rather than by drinks.

Deaths are reported with pure caffeine powder and tablets. Toxicity occurs at over 10 to 15 mg/kg, severe effects at over 40 mg/kg, and doses of 150 to 200 mg/kg (about 10 g in adults) can be fatal. One teaspoon of powder contains about 3 to 5 g.

Risk factors for harm. Powdered or concentrated products, pre-workout and weight loss supplements, co-use of stimulants, cardiac disease, pregnancy and hepatic impairment.

Course. Onset within 30 to 120 minutes; peak at 1 to 2 hours; the half life is about 5 hours and longer in liver disease, pregnancy and with oral contraceptives, so effects can last 12 to 24 hours.

Pathophysiology.

Caffeine blocks adenosine receptors, inhibits phosphodiesterase and mobilises intracellular calcium, causing catecholamine release and stimulation of the central nervous and cardiovascular systems.

Beta-2 stimulation causes vasodilatation and a shift of potassium into cells.

• Nausea, vomiting, abdominal pain, tremor, agitation, insomnia and tinnitus.
• Tachycardia, palpitations, supraventricular tachycardia, atrial fibrillation and ventricular arrhythmia.
• Hypotension (from beta-2 effects), hypokalaemia, hyperglycaemia, metabolic acidosis and rhabdomyolysis.
• Seizures, hallucinations, hyperthermia and cardiac arrest in severe cases.

Red flags.

• Ventricular arrhythmia, seizures or hypotension.
• Potassium under 2.5 mmol/L.
• Ingestion of powder or an unknown large amount.

• History of product, amount and time; co-ingested drugs; paracetamol and salicylate levels.
• ECG and continuous monitoring; potassium, magnesium, glucose, lactate, creatine kinase, renal function and blood gas.
• Serum caffeine level (over 80 mg/L suggests severe toxicity) if available; it should not delay treatment.
• Pregnancy test in women of childbearing age.

Differential diagnosis. Sympathomimetic or amphetamine toxicity, theophylline toxicity, thyrotoxicosis, serotonin toxicity, alcohol withdrawal and phaeochromocytoma.

• Activated charcoal 50 g orally once (1 g/kg, maximum 50 g, in children) within 1 hour of a significant ingestion if the airway is protected. Monitor the airway for aspiration. Avoid with reduced consciousness, ileus or gastrointestinal obstruction; no renal or hepatic adjustment; acceptable in pregnancy.
• Benzodiazepines for agitation and seizures: lorazepam 0.1 mg/kg intravenously (maximum 4 mg for each dose) over 2 minutes, repeated once after 5 to 10 minutes. Maximum 8 mg in total. Monitor breathing, oxygen saturation, blood pressure and sedation. Use lower doses in older adults, respiratory disease and hepatic impairment; use only when needed in pregnancy.
• Hypokalaemia: potassium chloride 20 mmol intravenously in 100 mL of 0.9% sodium chloride over 1 hour (central line for higher rates), repeated as needed. Maximum 40 mmol/hour with continuous ECG monitoring. Monitor potassium hourly and ECG. Avoid in renal failure and hyperkalaemia (potassium will rebound as caffeine clears); use caution to avoid overcorrection.
• Tachyarrhythmia and hypotension from beta stimulation: esmolol 500 micrograms/kg intravenously over 1 minute, then 50 micrograms/kg/minute infusion, increased by 50 micrograms/kg/minute every 5 minutes. Maximum 200 micrograms/kg/minute. Monitor blood pressure and heart rate continuously. Avoid in asthma, heart block and decompensated heart failure; reduce dose in older adults; use caution in pregnancy.
• Nausea: ondansetron 4 mg intravenously, repeated every 8 hours. Maximum 16 mg in 24 hours. Monitor QTc and potassium. Avoid in long QT syndrome; reduce dose to 8 mg daily in severe hepatic impairment.
• Intravenous fluids for hypotension and rhabdomyolysis; correct glucose and acidosis; cool for hyperthermia.
• Haemodialysis or haemoperfusion for severe poisoning: level over 80 mg/L, refractory arrhythmia, seizures or shock; haemodialysis removes caffeine effectively.
• Observe for at least 6 hours (12 to 24 hours for large ingestions or powder), with potassium and ECG normal before discharge.
• Psychiatric assessment in intentional ingestion; advice to avoid powdered caffeine.

Monitoring. Continuous ECG, potassium every 1 to 2 hours, glucose, temperature and neurological state.

Referral and escalation. Poisons information centre; intensive care for arrhythmia, seizures or shock; nephrology for dialysis.

Special groups. Pregnancy: slower clearance and foetal risk, so extend observation. Children: low thresholds for admission.